Routine surveillance for bacterial colonization has been used for the past three decades as a tool for the prediction of nosocomial infection in low birth weight infants; however, its usefulness has never been proven. A prospective cohort study was conducted to examine the utility of surveillance for pharyngeal colonization in detection and control of serious bacterial illness in low birth weight infants. One hundred fifty-four infants who weighed less than 1750 g and who were admitted to the Neonatal Intensive Care Unit were enrolled and followed for a total of 5620 infant-days. Pharyngeal cultures were collected at the time of enrollment and then weekly. All infants had bacterial pharyngeal colonization by the third day of life. Coagulase-negative staphylococci were the most common organisms cultured from the pharynx, followed by viridans streptococci and Staphylococcus aureus. More than 90% of the pharyngeal cultures grew multiple isolates. Gram-positive organisms, particularly coagulase-negative staphylococci, were the most prevalent organism recovered from blood and cerebrospinal fluid cultures. Fifty-two episodes of bacteremia and 6 episodes of cerebrospinal fluid infection occurred in 42 infants. Among infants with viridans streptococci in pharyngeal cultures, the subsequent risk of serious bacterial illness was significantly reduced (odds ratio = 0.16). However, pharyngeal cultures were poor predictors of the causative organism in an episode of serious bacterial illness. Pharyngeal and blood/cerebrospinal fluid cultures were concordant in only 11% of invasive infections. We conclude that pharyngeal surveillance cultures provide little clinically meaningful information and have no apparent utility in the Neonatal Intensive Care Unit setting.